Abstract |
Oxidative base damage occurs spontaneously due to reactive oxygen species generated as byproducts of respiration and other pathological processes in mammalian cells. Many oxidized bases are mutagenic and/or toxic, and most are repaired through the base excision repair pathway. Human endonuclease VIII-like protein 1 (hNEIL1) is thought to play an important role during the S phase of the cell cycle by removing oxidized bases in DNA replication fork-like (bubble) structures, and the protein level of hNEIL1 is increased in S phase. Compared with hNEIL1, there is relatively little information on the properties of the mouse ortholog mNEIL1. Since mouse cell nuclei lack endonuclease III-like protein (NTH) activity, in contrast to human cell nuclei, mNEIL1 is a major DNA glycosylase for repair of oxidized pyrimidines in mouse nuclei. In this study, we made mNEIL1-knockdown cells using an shRNA expression vector and examined the cell cycle-related variation in hydrogen peroxide (H2O2) sensitivity. Hypersensitivity to H2O2 caused by mNEIL1 knockdown was more significant in S phase than in G1 phase, suggesting that mNEIL1 has an important role during S phase, similarly to hNEIL1.
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Authors | Ryohei Yamamoto, Yukari Ohshiro, Tatsuhiko Shimotani, Mizuki Yamamoto, Satoshi Matsuyama, Hiroshi Ide, Kihei Kubo |
Journal | Journal of radiation research
(J Radiat Res)
Vol. 55
Issue 4
Pg. 707-12
(Jul 2014)
ISSN: 1349-9157 [Electronic] England |
PMID | 24706997
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology. |
Chemical References |
- RNA, Small Interfering
- Hydrogen Peroxide
- DNA Glycosylases
- NEIL1 protein, human
- Neil1 protein, mouse
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Topics |
- Animals
- Cells, Cultured
- DNA Damage
- DNA Glycosylases
(antagonists & inhibitors, genetics, metabolism)
- DNA Repair
(drug effects)
- G1 Phase
(drug effects)
- Gene Knockdown Techniques
- Humans
- Hydrogen Peroxide
(pharmacology)
- L Cells
- Mice
- RNA, Small Interfering
(genetics)
- S Phase
(drug effects)
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